儿童虐待与 NR3C1 外显子 1 甲基化、下丘脑-垂体-肾上腺轴失调和精神病理学的关联：系统综述。

Child maltreatment and NR3C1 exon 1 methylation, link with deregulated hypothalamus-pituitary-adrenal axis and psychopathology: A systematic review.

机构信息

I-Reach Lab, Unit of Clinical and Health Psychology, University of Fribourg, Switzerland.

出版信息

Child Abuse Negl. 2021 Dec;122:105304. doi: 10.1016/j.chiabu.2021.105304. Epub 2021 Sep 3.

DOI:10.1016/j.chiabu.2021.105304

PMID:34488052

Abstract

BACKGROUND

Epigenetics offers one promising method for assessing the psychobiological response to stressful experiences during childhood. In particular, deoxyribonucleic acid (DNA) methylation has been associated with an altered hypothalamus-pituitary-adrenal (HPA) axis and the onset of mental disorders. Equally, there are promising leads regarding the association between the methylation of the glucocorticoid receptor gene (NR3C1-1) and child maltreatment and its link with HPA axis and psychopathology.

OBJECTIVE

The current study aimed to assess the evidence of a link among child maltreatment, NR3C1-1 methylation, HPA axis deregulation, and symptoms of psychopathology.

METHODS

We followed the Prisma guidelines and identified 11 articles that met our inclusion criteria.

RESULTS

We found that eight studies (72.72%) reported increased NR3C1-1 methylation associated with child maltreatment, specifically physical abuse, emotional abuse, sexual abuse, neglect, and exposure to intimate partner violence, while three studies (27.27%) found no significant association. Furthermore, a minority of studies (36.36%) provided additional measures of symptoms of psychopathology or cortisol in order to examine the link among NR3C1-1 methylation, HPA axis deregulation, and psychopathology in a situation of child maltreatment. These results suggest that NR3C1-1 hypermethylation is positively associated with higher HPA axis activity, i.e. increased production of cortisol, as well as symptoms of psychopathology, including emotional lability-negativity, externalizing behavior symptoms, and depressive symptoms.

CONCLUSION

NR3C1-1 methylation could be one mechanism that links altered HPA axis activity with the development of psychopathology.

摘要

背景

表观遗传学为评估儿童时期应激经历的心理生物学反应提供了一种有前途的方法。特别是，脱氧核糖核酸（DNA）甲基化与下丘脑-垂体-肾上腺（HPA）轴的改变和精神障碍的发生有关。同样，关于糖皮质激素受体基因（NR3C1-1）甲基化与儿童虐待及其与 HPA 轴和精神病理学的关系之间的关联也有一些有希望的线索。

目的

本研究旨在评估儿童虐待、NR3C1-1 甲基化、HPA 轴失调和精神病理学症状之间关联的证据。

方法

我们遵循 Prisma 指南，确定了符合纳入标准的 11 篇文章。

结果

我们发现，八项研究（72.72%）报告了与儿童虐待相关的 NR3C1-1 甲基化增加，特别是身体虐待、情感虐待、性虐待、忽视和亲密伴侣暴力暴露，而三项研究（27.27%）发现没有显著关联。此外，少数研究（36.36%）提供了精神病理学症状或皮质醇的额外测量，以在儿童虐待的情况下检查 NR3C1-1 甲基化、HPA 轴失调和精神病理学之间的关联。这些结果表明，NR3C1-1 过度甲基化与 HPA 轴活性增加呈正相关，即皮质醇生成增加，以及精神病理学症状，包括情绪不稳定-负性、外化行为症状和抑郁症状。